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The role of TASK1 potassium channels in pulmonary hypertension following HIV infection

Supervisory team: Professor Alistair Mathie, Ms Emma Veale, Professor Ghazwan Butrous

Project details:
HIV infected patients have a > 10 fold higher incidence of pulmonary hypertension compared to the general population (e.g. Syed & Sani 2013, Heart 99 1146-1153), however the reason(s) underlying this is not clear. Recently the importance of the two-pore-domain potassium channel, TASK1, in pulmonary hypertension has been highlighted following the identification of an association between mutations in TASK1 and the disease in patients (Ma et al 2013, NEJM 369, 351-361). It is known that there is significant structural homology between the HIV-1 accessory protein Vpu and the N terminus of TASK1 and that the two proteins interact to disrupt each other’s function (Hsu et al 2004, Mol Cell 14, 259-267; Veale and Mathie unpublished observations). Using molecular biological, immunohistochemical and electrophysiological approaches, this project aims to determine the importance of this interaction in altering the functional properties of pulmonary arterial smooth muscles cells.

Funding notes:
This position is a University of Kent 50th Anniversary Scholarship and provides tuition fees, plus a maintenance allowance, for UK and EU nationals only. Applicants should possess (or expect to possess by the summer of 2015) at least an upper second class honours degree, or equivalent, in a subject related to the project. Experience in electrophysiology is desirable but not essential.

The project will commence in September 2015.

Interested applicants should send a CV and cover letter to Professor Alistair Mathie (a.a.mathie@kent.ac.uk) by 16 February 2015.  

CaSE Vacancy: Part-time paid Internship (3 months)

Part time: 0.6 FTE (3 days per week)
London Living Wage: £800 per month at 0.6 FTE (equivalent £1,335 per month pro rata)

The Campaign for Science and Engineering (CaSE) is the leading independent advocate for science and engineering in the UK. We are a membership organisation with an excellent track record of influencing policy and media at the highest levels, and focusing on the important and exciting issues facing the science and engineering sector.

We’re looking for someone to support our team on a fixed, short-term contract as a paid intern. The successful candidate will provide vital administration and communications support during an exciting and busy period for CaSE during the 2015 General Election. The intern will be responsible for contacts management, event management and communications support.

CaSE is a small organisation with big impact. It is fast-paced, fun, and operates at the highest levels of politics, business, academia and the media. Everyone at CaSE gives their all and we look to our intern candidates to do the same. In return, our interns benefit from the opportunity to experience everything we do first-hand and make a big contribution to a small team. We encourage our interns to develop as much as they can in an environment with unrivalled access and opportunity.
The deadline for applications is Midnight, 8 February 2015. Interviews will be held on 17 February in central London. We're looking for someone who can start around the beginning of March.

Full details of the role and how to apply

If you have any questions please contact Nick Hall.

PhD Studentship Project 

Role of intracellular and circulating microRNAs on post-cardiopulmonary acute kidney injury in a novel murine model

Supervisors:
Professor Gianni D Angelini, British Heart Foundation (BHF) Chair of Cardiac Surgery and Director of the NIHR Cardiovascular BRU, University of Bristol and Imperial College London G.D.Angelini@bristol.ac.uk
Professor Costanza Emanueli; BHF Senior Research Fellow, Bristol coordinator in the BHF Regenerative Medicine Centres, University of Bristol Costanza.Emanueli@bristol.ac.uk
Dr. Nishith Patel, clinical lecturer in Cardiac Surgery, Imperial College London nishith.patel@imperial.ac.uk

Acute kidney injury (AKI), defined as a reduction in estimated glomerular filtration rate (eGFR) of >25%, occurs in over 30% of cardiac surgery patients and is associated with a >4-fold increase in the odds of death as well as significant increases in resource use. There have been few advances in the treatment of this condition in the last 30 years and we have recently shown that clinical trials of therapeutic agents designed to ameliorate post cardiac surgery AKI have with few exceptions been unsuccessful. This is due in large part to our poor understanding of the underlying pathophysiological processes and the underpinning molecular pathways which is partly to the due absence of informative animal models allowing for basic science investigations. Notwithstanding, Patel and Angelini have recently developed a swine model of cardiopulmonary bypass (CPB)-induced AKI which has close homology to AKI in cardiac surgical patients. However, smaller animal models are necessary to integrate mechanistic research and test new therapeutic intervention.  

This project will focus on microRNAs (miRs). MiRs are small, non-coding RNAs able to target short (semi)complementary nucleotide sequences within the 3′ untranslated region (UTR) of messenger RNAs (mRNAs), thus post-transcriptionally inhibiting their expression. miRs are transcribed as a primitive form (pri-miR), which is next cleaved by the Drosha ribonuclease to produce a precursor miRNA (pre-miR), which  is further cleaved by Dicer to generate the mature miR.  A single miR is capable of targeting multiple mRNAs; conversely a single mRNA may contain multiple miR binding sites.  More than 1000 unique miRNAs have been identified within the human genome and it is suggested that one-third of expressed human genes contain miR regulatory target sites (http://www.mirbase.org/).  miRs have been implicated with several cardiovascular and renal pathologies and with diabetes.

The Emanueli laboratory leads on microRNAs at international level and is part of the Leducq Transatlantic Network on Vascular microRNAs (MIRVAD). She is currently focusing her microRNA work in the cardiac surgery setting, investigating the functional and biomarker roles of extracellular microRNAs and exosomes (nanovesicle used by microRNAs as a shuttle system).

This studentship project will:

  1. develop the new mouse model
  2. investigate the role of microRNAs and exosomes in CPB-induced AKI.

The student will be based at the Bristol Heart Institute, but he/she might be asked to spend a few months at the Imperial College London to set up the mouse model.

  • The PhD studentship is open to UK and European citizen, only.
  • A BSc with 2:1 (or equivalent) is the minimum requirement.  
  • We would be happy to receive interest from students who have already some laboratory experience, including for in vivo work.

Candidates should preliminary send their CVs and personal statement to the supervisors. If these are considered of interest, we’ll ask to provide reference letters.

We plan to initiate this project by June 2015.

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